Experimental Study Using Multiple Strains of Prion Disease in Cattle Reveals an Inverse Relationship between Incubation Time and Misfolded Prion Accumulation, Neuroinflammation, and Autophagy

Mammadova, Najiba; Greenlee, M. Heather; Moore, S. Jo; Sakaguchi, Donald; Greenlee, Justin; Sakaguchi, Donald

Experimental Study Using Multiple Strains of Prion Disease in Cattle Reveals an Inverse Relationship between Incubation Time and Misfolded Prion Accumulation, Neuroinflammation, and Autophagy

File

2020-Sakaguchi-ExperimentalStudy.pdf (3.33 MB)

Supplemental Files

Date

2020-07-01

Authors

Mammadova, Najiba

Greenlee, M. Heather

Moore, S. Jo

Sakaguchi, Donald

Greenlee, Justin

Sakaguchi, Donald

Authors

Person

Sakaguchi, Donald

Director of Biology and Genetics Undergraduate Program and Morrill Professor

Organizational Units

Organizational Unit

Biomedical Sciences

The Department of Biomedical Sciences aims to provide knowledge of anatomy and physiology in order to understand the mechanisms and treatment of animal diseases. Additionally, it seeks to teach the understanding of drug-action for rational drug-therapy, as well as toxicology, pharmacodynamics, and clinical drug administration.

History
The Department of Biomedical Sciences was formed in 1999 as a merger of the Department of Veterinary Anatomy and the Department of Veterinary Physiology and Pharmacology.

Dates of Existence
1999–present

Related Units

College of Veterinary Medicine (parent college)
Department of Veterinary Anatomy (predecessor, 1997)
Department of Veterinary Physiology and Pharmacology (predecessor, 1997)

Organizational Unit

Immunobiology

The Immunobiology graduate program welcomes you to explore the opportunities for integrative graduate research and study toward an MS or PhD degree from Iowa State University. Our unique program includes diverse faculty expertise and flexible choices for individual specializations within the dynamic field of Immunobiology.

Organizational Unit

Neuroscience

The Graduate Program in Neuroscience is an interdepartmental and interdisciplinary training program at Iowa State University that offers the Master of Science and Doctor of Philosophy degrees. The Neuroscience training program offers a broad spectrum of Neuroscience research opportunities, ranging from the molecular to the cellular to the systems level of analysis. The program includes over 40 faculty from the departments of Biochemistry, Biophysics and Molecular Biology; Biomedical Sciences; Chemical and Biological Engineering; Ecology, Evolution, and Organismal Biology; Food Science and Human Nutrition; Genetics, Development and Cell Biology; Kinesiology; Mechanical Engineering; and Psychology.

Organizational Unit

Genetics, Development and Cell Biology

The Department of Genetics, Development, and Cell Biology seeks to teach subcellular and cellular processes, genome dynamics, cell structure and function, and molecular mechanisms of development, in so doing offering a Major in Biology and a Major in Genetics.

History
The Department of Genetics, Development, and Cell Biology was founded in 2005.

Related Units

College of Agriculture and Life Sciences (parent college)
College of Liberal Arts and Sciences (parent college)

Department

Biomedical SciencesImmunobiologyNeuroscienceGenetics, Development and Cell Biology

Abstract

Proteinopathies result from aberrant folding and accumulation of specific proteins. Currently, there is a lack of knowledge about the factors that influence disease progression, making this a key challenge for the development of therapies for proteinopathies. Because of the similarities between transmissible spongiform encephalopathies (TSEs) and other protein misfolding diseases, TSEs can be used to understand other proteinopathies. Bovine spongiform encephalopathy (BSE) is a TSE that occurs in cattle and can be subdivided into three strains: classic BSE and atypical BSEs (H and L types) that have shorter incubation periods. The NACHT, LRR, and PYD domains–containing protein 3 inflammasome is a critical component of the innate immune system that leads to release of IL-1β. Macroautophagy is an intracellular mechanism that plays an essential role in protein clearance. In this study, the retina was used as a model to investigate the relationship between disease incubation period, prion protein accumulation, neuroinflammation, and changes in macroautophagy. We demonstrate that atypical BSEs present with increased prion protein accumulation, neuroinflammation, and decreased autophagy. This work suggests a relationship between disease time course, neuroinflammation, and the autophagic stress response, and may help identify novel therapeutic biomarkers that can delay or prevent the progression of proteinopathies.

Comments

This article is published as Mammadova, Najiba, M. Heather West Greenlee, S. Jo Moore, Donald S. Sakaguchi, and Justin J. Greenlee. "Experimental study using multiple strains of prion disease in cattle reveals an inverse relationship between incubation time and misfolded prion accumulation, neuroinflammation and autophagy." The American Journal of Pathology 190 (2020):1461-1473. doi: 10.1016/j.ajpath.2020.03.006. Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.